Tetrahedral DNA Enhanced Antibacterial Effect of Lysozyme

Lysozyme (Lys) is a potential candidate to address the issue of drug-resistant bacteria with conventional antibiotics. However, its weak killing effect on Gram-negative bacteria hinders its prospect for clinical application. To solve this problem, we modified lysozyme using a tetrahedral framework nucleic acid (TDN) to construct its complex (TDN-Lys). With the help of TDN, lysozyme showed a great bactericidal effect against both drug-resistant bacteria, MRSA, and Gram-negative bacteria, E. coli O157:H7. Morphological examination showed that TDN-Lys disrupted the external cell wall of bacteria more severely than did free lysozyme. Furthermore, TDN-Lys effectively healed MRSA-infected wounds in mice. Single-molecule force spectroscopy experiments revealed for the first time at the molecular level that TDN has a stronger affinity toward bacteria surface than lysozyme, which demonstrated that carriers or modified adjuvants with higher bacterial affinity can enhance lysozyme's antibacterial activity. Our method provides a feasible strategy against bacterial drug resistance.